Two Forms of IGF-1: Muscle-liver & Mechano Growth Factor

Two forms of IGF-1 have been discovered that have different mechanisms of action. The first form, IGF-1Ea, has a similar structure to the major form produced in the liver. It’s been termed the muscle-liver type IGF-1 as it’s produced not only in the liver, but in muscle as well. The other form of IGF-1 has been termed IGF-1Ec, also known as Mechano Growth Factor (MGF), as it’s only markedly upregulated in response to exercise and/or muscle damage. Both MGF and muscle-liver type IGF-1 are increased in muscle in response to muscle loading, but have different biological effects. In vitro (test tube) studies have shown that when MGF is added to muscle satellite cells, the cells rapidly increase in number, but they don’t become mature muscle stem cells until muscle-liver IGF-1 is added to the test tube. When muscle-liver IGF-1 is added, it causes an increase in cell density and satellite cells fuse with muscle fibers.17 MGF’s main role is to initiate satellite cell activation to kick-start the muscle growth process, while muscle-liver type IGF-1 promotes differentiation of immature satellite cells into mature muscle fibers.7 MGF is expressed before muscle-liver type IGF-1 in muscle, which suggests that they work independently of each other.


Recent research has shown that MGF is expressed in muscle soon after damage, which occurs at the same time satellite cells become activated. MGF is considered the “growth pulse” that activates the initial spark to activate satellite cells, but it lasts just a few days. Later, several days after the initial muscle damage, MGF levels begin to decline while muscle-liver type IGF-1 levels start to rise in muscle (research suggests 7-11 days later). It’s thought that the MGF gene is expressed first, then is spliced toward the muscle-liver type IGF-1, which is more abundant in muscle and therefore, the major supplier of mature IGF-1, which upregulates protein synthesis.8
GH has been shown to produce large increases in serum IGF-1 from the liver, yet muscle hypertrophy from GH alone is controversial and modest at best, but the serum levels of IGF-1 in the blood are a fraction of the muscle-produced IGF-1 levels.10 When GH was administered to elderly men, there were large increases in liver-muscle specific IGF-1, with only small increases in MGF.10 This could be the reason GH has such a poor effect on increasing muscle hypertrophy, as a more specific drug that increases MGF is needed.


Testosterone is a potent stimulator of muscle hypertrophy, as there’s a dose-dependent increase in muscle fiber hypertrophy and satellite cell number. Testosterone-induced skeletal muscle hypertrophy is associated with increased satellite cell replication and activation.19 The big question that needs to be researched is, “Does testosterone increase MGF”? So, what happens when you compare MGF and muscle-liver type IGF-1 head-to-head? Although both have anabolic effects in muscle, muscle-liver type IGF-1 takes months to develop muscle hypertrophy, while MGF makes the same increase in muscle mass in a few weeks.